Adverse events related to use of opioid analgesics are widespread in the US, compromising a large and growing fraction of all medication-related patient safety events. Opioids account for the majority of deaths related to prescription drug overdoses in the US each year. While opioids represent a typical component of pain treatment regimens following most surgical procedures, available evidence suggests that excessive opioid prescribing after surgery may contribute to drug diversion, abuse, and harm. Few data exist to characterize the large-scale patient safety implications of opioid prescribing practices after surgical procedures. As short-term pain treatment with opioids can lead to persistent use, dependence, and associated harm, postoperative pain management decisions hold major potential consequences for patients and society at large. In this context, major evidence gaps including: (1) which patients are at greatest risk of becoming new long-term opioid users following an initial exposure at the time of surgery, (2) what time period represents the transition point from acute use to persistent use, and (3) which clinical and policy interventions reduce the likelihood of persistent use among surgical patients. The proposed project will take advantage of a unique international collaboration between US and Canadian researchers; our project will fill a critical need by identifying opportunities before, during, and after the surgical care episode that can pre-empt or interrupt the path towards iatrogenic addiction and opioid-related harm. Our aims are: (1) To identify groups of patients not previously receiving opioids for non-cancer pain who become new persistent opioid users during the first year following a surgical procedure and to understand the timing of the transition to persistent use; (2) To test the impact of acute postoperative pain management strategies on the risk of new long-term opioid use and associated adverse drug events in the first year after surgery, including different opioid prescribing patterns and different anesthetic approaches, and (3) To test the impact of state, province, and national opioid prescribing policies on the risk of new long- term opioid use and associated adverse drug events in the first year after surgery. Ultimately, this project will yield critical insights into patterns and predictors of patient safety events related to postoperative opioid use after surgery and provide information to guide the development of clinical and policy interventions to improve the safety of perioperative care in the US and elsewhere.